The goal of this project is to determine the range and mechanism of action of phytoestrogens (genistein, diadzein and soy extracts) on innate immune function via estrogen receptor-dependent and independent pathways. This goal will be accomplished using estrogen receptor deficient (ERKO) severe combined immunodeficient (SCID) mouse models of bacterial inflammation in the gut, liver and spleen. The hypothesis is that estrogen and phytoestrogen signaling is a positive regulator of macrophage and natural killer cell function. Specifically, the project will... 1) Determine the effects of the loss of estrogen receptor alpha signaling on bacterial-induced inflammation. 2) Determine the effects of the loss of estrogen receptor beta signaling on bacterial-induced inflammation. 3) Determine the effects of the loss of estrogen receptors alpha and beta signaling on bacterial induced inflammation. The PI on this project is D. Mark Estes and the co-PI is Criag Franklin. Two consultants on the project are Helen Mullen and Dennis Lubahn. All of these personnel are based at the University of Missouri-Columbia. The sites for the research are the UM-C?s Horticulture and Agroforestery Research Center in New Franklin and the UM-C?s Southwest Research Station in Mt. Vernon.